Science Focus on industry members

BY NICK ZAGORSKI

In this annual Science Focus feature, we profile a few of our members who are doing industrial research.

All American Society for Biochemistry and Molecular Biology members share a passion for the biochemical sciences, but the methods by which these scientific passions are fulfilled are exceptionally varied. This is especially true among members who work in industry. From small startups that many people have not yet heard of to global biotech giants like Merck and Invitrogen and even nonpharmaceutical companies like Kraftand Coca-Cola, ASBMB scientists are making important contributions. In this annual Science Focus feature, we once again profile a small sampling of these industrious individuals to showcase the rich and diverse scope of ASBMB research.

Nancy Robinson

Although people generally do their best to avoid trips to the hospital, at some point in life most everyone will require a surgical or diagnostic procedure. And in those moments, we expect that both our physicians and their equipment be of the best quality.

Nancy Robinson has the satisfaction of knowing that through her work to improve methods to decontaminate and sterilize surgical instruments for reuse, the tools used in various surgical procedures will meet the patient's expectation of best quality.

“Some of my colleagues have kidded me that I had fallen from the true faith when I left academia,” Robinson says. “But that is not the case; here at STERIS I have found an outlet for my passion of solving technical challenges and my desire to achieve tangible outcomes.”

At first thought, a medical device company – as compared to a pharmaceutical company – may seem like an unusual destination for a biochemist looking for a career in the private sector. However, STERIS, where Robinson has been since 1998, is really not too different from a drug company. Both places bring together diverse scientists to solve a biological problem and bring it to market; both involve working through U.S. Food and Drug Administration regulations to ensure that final products are safe and effective; and perhaps most importantly, both groups are about improving human lives.

At STERIS, Robinson carries out research in the Infection Prevention Technologies branch of the health-care business unit, which develops reprocessing equipment such as sterilizers, washer-disinfectors, high-level disinfectants and automated liquid chemical processing systems. (STERIS also has another health-care branch that offers surgical lights, tables and other equipment.)

For the past several years, her team of dedicated chemists and microbiologists, working with a group of talented engineers, has been designing and improving low temperature vaporized hydrogen peroxide sterilization systems called the Amsco® V-PRO™ 1 and the V-PRO 1 Plus Low Temperature Sterilization Systems. Such technology is critical for rapid reprocessing of heat-sensitive instruments that cannot handle the rigors of steam sterilization.

For the past several years, Nancy Robinson has been designing and improving low temperature vaporized hydrogen peroxide sterilization systems called the Amsco® V-PRO™ 1 and the V-PRO 1 Plus Low Temperature Sterilization Systems.

Recently promoted to senior director, Robinson devotes much of her time to carrying out the verification and validation testing of the products and interacting with various global regulatory bodies through the submission process.

It may sound bureaucratic, but Robinson counters that it is quite interesting. “It is very rewarding to interact with both our customers and the medical device manufacturers and discuss how to improve the ease, quality and outcome of their work,” she says. “It’s also rewarding and a bit challenging to sort through the different global regulatory requirements for our products and devise strategies to most effectively meet them.”Robinson admits, though, that she didn’t envision this type of job description back when she re-entered the science workforce in 1994 following a four-year break to raise her children. Previously, she had completed her graduate studies in enzymology and done a commission with the United States Army Medical Research Institute of Infectious Diseases studying the metabolism of a small cyclic peptide toxin called microcystin-LR. (Robinson had received a U.S. Army college scholarship.)

She initially took a postdoctoral position at Case Western Reserve University – where she had also received her doctorate – to study the structure of the cornified envelope, the protective protein coating formed by the upper layers of skin. Robinson’s plan was to obtain a permanent position in either academia or industry within four years.

“To that end I was exploring teaching at local institutions, writing grants to develop independent support and reminding colleagues as they would move on to other positions to keep me in mind if anything opened up at their new workplace,” she says.

“Things were moving along, and I had just heard from a local university about a potential job when I received a call from a former colleague about an opening at STERIS,” Robinson continues. “I was leaning toward academia, but my colleague talked me into coming for a visit.”

“After my interview with STERIS, I began to lean the other way.”

While Robinson enjoyed basic research, she realized what really drove her in the lab was problem solving and that she preferred tangible solutions to discovery for discovery’s sake.

Thirteen years later, she remains excited about working in this challenging and fast-paced industry environment. “I continue to expand my knowledge base every day, I get to work with a great team of colleagues, and I can say I have never regretted my decision to join.”

Juan Manuel Domínguez

While visitors to Madrid can surround themselves with a culture rich in art, history and architecture, they also can find some newly emerging science culture if they look in the right spots. One such place is found some 10 miles outside the city, in secluded Tres Cantos – the headquarters of Noscira.

One of many small, independent biotech companies springing up in Spain, Noscira is a reflection of Spain’s new scientific ambitions.

“Spain does not have a long tradition of venture-fueled biotech companies,” notes Juan Manuel Domínguez, who heads Noscira’s drug discovery department, “so companies like ours have trouble securing financing. Investors aren’t used to supporting an enterprise that, even if highly successful, won’t bear fruit for many years.”

But if some of the early biotech startups like Noscira, founded back in 2000, can achieve their goals, that can build confidence for future companies.

And as of now, Noscira, which uses natural marine products to identify new therapeutic drugs for Alzheimer’s and other neurodegenerative diseases, is on track to provide a boost of that confidence. It’s currently exploring the potential benefit of a compound called tideglusib in phase II clinical trials for both Alzheimer’s and progressive supranuclear palsy.

It’s a tremendous feeling for Domínguez, who joined Noscira in 2008. “Compared to a large company, working at Noscira (with only around 60 full time employees) offers everyone a true sense of ownership in the whole drug discovery and development process.”

Domínguez understands the contrast quite well, having spent 16 years working at GlaxoSmithKline before his move to Noscira (a very short move, as GSK happens to have a drug discovery center in the same town as Noscira).

He joined the global pharma giant straight out of graduate school, earning his doctorate degree in chemistry from the Complutense University of Madrid. “My graduate mentor had many connections with industry people and often took his pupils to visit several companies’ facilities, which gave me good opportunity to see what an industry career would be like,” Domínguez says. “I thought industry would be a great place to pursue my interests in enzymology, and I had good timing as Glaxo just opened a new center in Spain when I finished my Ph.D.”

Noscira has a library of over 20,000 natural products extracted from various marine organisms, including starfish.

His early work in Glaxo’s biochemistry department involved studying the mode of action for various novel antifungal agents to understand how they specifically targeted fungi but not other eukaryotes. His work retained quite a bit of academic flavor, but he did begin to see some of the differences of working in industry compared to a university.

“I’m not saying it’s a good or bad thing, but working at a biotech or pharma does require a scientist to be more pragmatic about his projects,” he notes. “So if anyone is thinking about going into the industry sector, they should take into account that sometimes they have to let promising experiments go.”

In 2001, following the merger of Glaxo and SmithKline Beecham (which also had a center in Tres Cantos), he moved on to the assay development team. His specialty was developing and miniaturizing assays for hard-to-obtain proteins; during that time he managed to develop a process for assaying substrates of fatty acid synthase – which is very hard to prepare in large quantities – that only required 3 ml sample sizes.

Those skills in protein biochemistry and running assays are valuable for Noscira, which has a library of more than 20,000 marine natural extracts for screening. Equally valuable has been the international exposure Domínguez received in his nearly two decades at GSK; though he has spent most of his time in his hometown of Madrid, Domínguez has worked in laboratories throughout Europe and the U.S. That international interaction has given Domínguez important perspectives on success.

“In the United States, for example, which has a long history in the pharmaceutical industry, I’ve seen successful places often have matrix management with a strong horizontal leadership,” he says. “That is, a senior executive will listen to junior researchers because they have the in-depth knowledge about studies, and this is less common in Europe, where hierarchy is still quite vertical.”

But the scientific talent certainly is there, and with a little time, Domínguez thinks the mindset will shift as well. Soon, Spain’s homegrown biotechs will be as highly regarded as its many other cultural contributions.

Mary Bossard

As she prepared to graduate from high school, Mary Bossard received an interesting offer from her father. “He agreed to pay for my college education, so long as I picked a major with which, in his words, I could earn a living.”

Perhaps not the most romantic way to enter the world of chemistry, but in the end the deal has certainly worked out in Bossard’s favor. At Nektar Therapeutics in the underrated science hub of Hunstville, Ala., Bossard not only has made a living but also has found a stimulating environment where she can pursue academic and applied challenges while developing new polyethylene glycol-conjugated molecules to treat a variety of diseases.

Initially, Bossard thought that her career would follow a purely academic path, believing that was the only viable option. Raised and educated in the American heartland (the native Iowan earned her bachelor’s degree from Central College in Pella, Iowa, and her doctorate at the University of Nebraska-Lincoln), her exposure to industry chemistry was limited to the industrial and agricultural sectors.

But then a new world opened during her postdoctoral fellowship – which, like college, ended up as a brokered deal.

“My advisor had suggested moving away from the Midwest, so I thought it would be great to go to a foreign country; but my husband stipulated that our destination country had to speak English,” she notes.

“So we ended up in California.”

At Judith Klinman’s laboratory at the University of California, Berkeley, to be exact; and during that time, Bossard attended an ASBMB meeting in San Francisco and saw a poster from Monsanto researchers detailing mechanistic studies of inhibitors for plant enzymes.

“The work was similar to my own enzyme studies in animals,” she says, “except for the fact that I had to make my own radiolabeled substrates and inhibitors while they had a department which synthesized them.”

Envy aside, Bossard realized that industry did offer a broad spectrum of research pursuits.

She first started down that path as a bench chemist at Smith, Kline & French (now GlaxoSmithKline) near Philadelphia studying enzymatic drug targets. After several years, she got an opportunity to move closer to home and try something different at a small, private company in Lincoln called Bio Nebraska. There, she used enzymes as reagents instead of targets to create and modify recombinant peptides.

At Nektar, Mary Bossard focuses on PEG therapeutics.

“I viewed this period almost like a training exercise,” she says. “I developed new skills, got exposure to the downstream side of research and manufacturing, and learned how to write research methods, batch records and reports to support a GMP manufacturing process.”

The constant risk, of course, was that the small company might run out of money, which eventually happened in 2002. However, a search consultant soon called her up with a job description that sounded absolutely great. Then he added that it was in Alabama.

“I replied that there weren’t any pharmaceutical companies in Alabama, and the consultant clarified that Shearwater Polymers was technically considered a drug delivery company, but the job requirements fit very well with my skill sets.”

At the time Bossard joined, Shearwater Polymers (owned by Inhale) was primarily a catalog business that designed and provided PEG reagents to pharmaceutical companies for protein conjugation work; a lot of her early work involved traveling with the business teams to perform PEG dog-and-pony shows. Over the years, the company changed its name to Nektar and adapted its business model and now focuses on PEG therapeutics instead of reagents.

“We don’t carry out de novo drug discovery but rather take known entities that have some level of clinical validation and make chemical improvements,” she explains. We develop some PEGylated molecules on our own while also partnering with other companies to help them get protein conjugates into the clinic faster than they would have done working on their own.” One partner, Baxter, is submitting the European equivalent of an IND to test a new PEGylated blood factor for hemophilia A in the clinic this summer.

As senior fellow, Bossard now primarily leads teams; she oversees all of the partner protein projects and the in-house protein platform work that addresses the mechanistic questions about how and why the protein conjugates work.

“It was a blind plunge when I first came here in 2002,” she says, noting that the words “drug delivery” and “Alabama” never crossed her mind when she began looking for a new job. But she ended up following an important mantra that she considers good advice for other young scientists thinking about industry: “You have to be open to new opportunities and let the organization speak for itself.”